Micrototal analysis systems (μTAS), which have also been termed “chemical laboratories on a chip,” are being developed to enable the rapid and sensitive detection of particular chemicals and biochemicals, including pollutants, high explosives, chemical and biological warfare agents, and genomic and proteomic materials. Micrototal analysis systems enable vast improvements in cost, speed, sample and reagent usage, and sample throughput by the integration of fluid manipulation and the different steps of an analytical process into a single microfluidic device. In particular, the microfluidic device seeks to integrate the analytical steps of sample injection, pretreatment, separation, and detection on a single microchip.
A sample to be analyzed generally undergoes sample preparation or pretreatment prior to an actual analysis. Sample pretreatment may involve extracting the sample from a matrix, purification of the sample to remove interferents, derivatization to make the sample more detectable, or analyte preconcentration. In particular, a sample preconcentrator can serve the important function of collecting, purifying, and boosting the concentration of a target analyte to improve detection capability and to discriminate against interferents. Especially for trace analysis, preconcentration of target analytes may enable orders-of-magnitude concentration enhancements, thereby easing separation and detector sensitivity requirements. However, the integration of sample pretreatment into microfluidic devices remains one of the major hurdles to the miniaturization of μTAS. Integration of the sample pretreatment with the microfluidic device is particularly challenging due to the requirement to localize specific analytes from an open flow system and the wide variation and complexity of the samples that need to be analyzed. See e.g., Lichtenberg et al., “Sample pretreatment on microfabricated devices,” Talanta 56, 233 (2002).
Preconcentrators for μTAS have typically used a passive stationary phase or sorptive medium to retain the analyte for subsequent elution in a more concentrated form. Preferably, the sorptive medium can selectively extract and isolate the target analyte while having a low affinity for other compounds and interferents in the sample stream. Microfluidic systems for manipulating biological fluids have consisted of passive chromatographic media that selectively adsorb solution species, such as proteins, to promote preconcentration or other functions. However, such passive preconcentrators may not provide sufficiently rapid switching to keep up with the fluid flow rate requirements of the separation and detection steps of the μTAS.
The present invention comprises a biological preconcentrator in which the adsorption and desorption processes are actively switched in response to external stimulation. The critical components required to perform the active switching include an active film whose surface properties can be made to change in response to controlled external stimulation and an integrated platform that can provide the appropriate stimulus to the active film within a fluidic environment.